Identifying sources of infection and establishing source control is an essential component of the workup and treatment of sepsis. Investigation with history, physical examination, laboratory tests, and imaging can in identifying sources of infection. All organ systems have the potential to develop sources of infection. However, there are inherent difficulties presented by some that require additional diligence, namely, urinalysis, chest radiographs, and intraabdominal infections. Interventions include administration of antibiotics and may require surgical or other specialist intervention. This is highlighted by the Surviving Sepsis Campaign with specific recommendations for time to antibiotics and expeditious time to surgical source control.